PRKAA2 Gene

Name	protein kinase, AMP-activated, alpha 2 catalytic subunit
Description	The protein encoded by this gene is a catalytic subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. Studies of the mouse counterpart suggest that this catalytic subunit may control whole-body insulin sensitivity and is necessary for maintaining myocardial energy homeostasis during ischemia. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPRKAA2 – the gene encoding the catalytic α2‐subunit of AMP‐activated protein kinase (AMPKα2) – plays a central role in sensing energy stress and orchestrating metabolic adaptations. In skeletal muscle, for example, AMPKα2 activity increases in response to progressive exercise intensity, favoring enhanced fatty acid oxidation and improved substrate metabolism, while its activation is attenuated by high glucose availability during exercise. These findings support a model wherein PRKAA2 enables muscle cells to rapidly adjust energy fluxes under varying nutritional conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its crucial role in skeletal muscle, PRKAA2 is important in cardiovascular and oncologic contexts. Studies using dominant‐negative AMPKα2 in cardiomyocytes have shown that dampening of PRKAA2 activity contributes to the development of cardiomyopathy, while low expression levels of AMPKα2 in hepatic tumors are associated with undifferentiated phenotypes and poor clinical outcomes, underscoring its tumor‐suppressive potential. Complementary genetic analyses have further linked PRKAA2 polymorphisms to insulin resistance and type 2 diabetes, highlighting the multifaceted influence of AMPKα2 on cellular growth and metabolic stability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond these roles, PRKAA2 is also implicated in the metabolic adjustments associated with aging and hypoxic stress. In older individuals, a decline in AMPKα2 activity may contribute to impaired metabolic homeostasis, whereas activation of AMPKα2 by exercise‐regulated adipomyokines (such as meteorin‐like) has been shown to improve glucose tolerance. In hypoxic tumor models, increased expression and nuclear redistribution of AMPKα2 further emphasize its involvement in mediating cellular adaptation to oxygen deprivation, thus integrating stress signals with transcriptional and metabolic responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhi-Ping Chen, Terry J Stephens, Sid Murthy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of exercise intensity on skeletal muscle AMPK signaling in humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/diabetes.52.9.2205"}], "href": "https://doi.org/10.2337/diabetes.52.9.2205"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12941758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12941758"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Thorbjorn C A Akerstrom, Jesper B Birk, Ditte K Klein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oral glucose ingestion attenuates exercise-induced activation of 5'-AMP-activated protein kinase in human skeletal muscle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.02.057"}], "href": "https://doi.org/10.1016/j.bbrc.2006.02.057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16598851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16598851"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ferhaan Ahmad, Michael Arad, Nicolas Musi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased alpha2 subunit-associated AMPK activity and PRKAG2 cardiomyopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.105.550806"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.105.550806"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16275868"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16275868"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chi-Wai Lee, Leo Lap-Yan Wong, Edith Yuk-Ting Tse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-12-0429"}], "href": "https://doi.org/10.1158/0008-5472.CAN-12-0429"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22728651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22728651"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Momoko Horikoshi, Kazuo Hara, Jun Ohashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A polymorphism in the AMPKalpha2 subunit gene is associated with insulin resistance and type 2 diabetes in the Japanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/diabetes.55.04.06.db05-0727"}], "href": "https://doi.org/10.2337/diabetes.55.04.06.db05-0727"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16567511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16567511"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mengyao Li, Lex B Verdijk, Kei Sakamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced AMPK-ACC and mTOR signaling in muscle from older men, and effect of resistance exercise."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mech Ageing Dev (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mad.2012.09.001"}], "href": "https://doi.org/10.1016/j.mad.2012.09.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23000302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23000302"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jung Ok Lee, Won Seok Byun, Min Ju Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKα2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/febs.15301"}], "href": "https://doi.org/10.1111/febs.15301"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32196931"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32196931"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kathryn M Neurath, Martin P Keough, Tom Mikkelsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AMP-dependent protein kinase alpha 2 isoform promotes hypoxia-induced VEGF expression in human glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glia (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/glia.20326"}], "href": "https://doi.org/10.1002/glia.20326"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16518831"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16518831"}]}]}]}
Synonyms	PRKAA, AMPKA2, AMPK2
Proteins	AAPK2_HUMAN
NCBI Gene ID	5563
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PRKAA2 has 8,037 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 137 datasets.

Click the + buttons to view associations for PRKAA2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PRKAA2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PRKAA2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PRKAA2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PRKAA2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PRKAA2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PRKAA2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PRKAA2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving PRKAA2 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PRKAA2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PRKAA2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PRKAA2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PRKAA2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PRKAA2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PRKAA2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with PRKAA2 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PRKAA2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PRKAA2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PRKAA2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PRKAA2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of PRKAA2 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PRKAA2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PRKAA2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PRKAA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PRKAA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PRKAA2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PRKAA2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PRKAA2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PRKAA2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PRKAA2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PRKAA2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with PRKAA2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PRKAA2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PRKAA2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for PRKAA2 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with PRKAA2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PRKAA2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PRKAA2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with PRKAA2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with PRKAA2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with PRKAA2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for PRKAA2 protein from the curated DrugBank Drug Targets dataset.